GBM News: “Achilles Heel” of Glioblastoma Found? - NFCR
Donate Now
Give in Honor or Memory Donate Now

Blog

“Achilles Heel” of Glioblastoma Found?

October 21, 2019 NFCR Writer David Perry Blog, Rare Cancer

glioblastoma achilles heel

Glioblastoma, also known as glioblastoma multiforme (GBM), is a type of primary brain cancer. It arises in brain cells called astrocytes, a type of supportive (glial) cell that composes the connecting tissue of the brain. GBM is also one of the most challenging cancers to cure due to its resistance to existing drug therapies, it is also notoriously difficult to remove completely via surgery. About 25 percent of children with this type of cancer live five years or longer, while the median survival time for adults with glioblastoma is 15 to 16 months with surgery, chemotherapy, and radiation treatment.

Now an intriguing front in the battle against GBM has recently opened: a research group headed by Professor Pirjo Laakkonen at the University of Helsinki in Finland had already found that the expression of a small fatty acid-binding protein (MDGI, or FABP3) in glioblastoma cells increases their ability to invade tissues and is linked with a poorer prognosis for the patient. Further investigations of the mechanism leading to cell death revealed that silencing MDGI caused changes in the phospholipid (any of a group of fatty compounds) composition of the lysosomes in glioblastoma cells. The absence of MDGI caused instability in the membranes of lysosomes, cleaning organelles found inside tumor cells, which, in turn, resulted in the leakage of acidic and proteolytic enzymes contained in the lysosomes into the cytoplasm, initiating cell death.

“Our new research revealed that glioblastoma cells depend on the expression of a gene which produces the MDGI protein. Inhibiting the function of this gene results in the death of the tumor cells,” Laakkonen explained in a press release.

What’s more, this finding is particularly interesting because the cell death caused by leakage in the lysosomes of glioblastoma cells can be activated by using drugs that cross the blood-brain barrier. In their studies, Laakkonen’s group used an antihistamine known as clemastine. By no means new or experimental, clemastine was patented in 1960, and has been in use since 1967 to treat relieve hay fever; it was approved by the FDA as an anti-allergenic in 1977 and has been on the market since 1993 in generic forms.

In cell cultures, clemastine resulted in lysosome-mediated cell death in glioblastoma cells already at concentrations which had no significant effect on healthy cells of different types. In mouse models, clemastine was very effective in reducing the spread of brain tumors and improving the survival rate of the animals. In the case of the most invasive brain tumor model, the administration of clemastine resulted in the disappearance of the entire tumor. That the delivery method of Laakkonen’s process involves a well-known drug already approved by the FDA may well speed it through subsequent medical trials.

“Our findings demonstrate that antihistamines and other drugs that increase the permeability of the lysosomal membrane can be considered as an enhancing therapy for patients with glioblastoma alongside established treatments,” says Laakkonen.

GBM AGILE

Glioblastoma Multiforme (also known as GBM) is the deadliest brain cancer and is widely regarded as incurable and universally fatal, killing 95% of patients within five years of diagnosis. NFCR is part of a robust, international coalition working on innovative ways to research the disease. Learn more here: https://www.nfcr.org/research-programs/research-focus-areas/gbm-agile/.

References
Fischer, Jnos; Ganellin, C. Robin. (2006). Analogue-based Drug Discovery. Retrieved from: https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA547#v=onepage&q&f=false
Healthline.com. (2019). What is Glioblastoma? Retrieved from: https://www.healthline.com/health/brain-tumor/glioblastoma
La Bastide, Danielle. (2017). An Over-The-Counter Allergy Drug Is Reversing Damage Done by Multiple Sclerosis. Retrieved from: https://interestingengineering.com/an-over-the-counter-allergy-drug-is-reversing-damage-done-by-multiple-sclerosis
University of Helsinki. (2019). Re­search­ers dis­cover the Achilles’ heel of an ag­gress­ive brain can­cer – could an­ti­histam­ine be a po­ten­tial aid in de­feat­ing can­cer­ous cells? Retrieved from: https://www.helsinki.fi/en/news/health-news/researchers-discover-the-achilles-heel-of-an-aggressive-brain-cancer-could-antihistamine-be-a-potential-aid-in-defeating-cancerous-cells

Comments(10)

  1. REPLY
    Marcos Escosa says
    October 24, 2019 at 11:38 am

    Good morning
    The current clinical care of glioblastomas leaves behind invasive, radio‐ and chemo‐resistant cells. Recently mammary‐derived growth inhibitor (MDGI/FABP3) has been identified as a biomarker for invasive gliomas. This is a novel function for MDGI in the maintenance of lysosomal membrane integrity, thus rendering invasive glioma cells unexpectedly vulnerable to lysosomal membrane destabilization. MDGI silencing impaired trafficking of polyunsaturated fatty acids into cells resulting in significant alterations in the lipid composition of lysosomal membranes, and subsequent death of the patient‐derived glioma cells via lysosomal membrane permeabilization (LMP). In a preclinical model, treatment of glioma‐bearing mice with an antihistaminergic LMP‐inducing drug efficiently eradicated invasive glioma cells and secondary tumours within the brain. This unexpected fragility of the aggressive infiltrating cells to LMP provides new opportunities for clinical interventions, such as re‐positioning of an established antihistamine drug, to eradicate the inoperable, invasive, and chemo‐resistant glioma cells from sustaining disease progression and recurrence.
    Dr. Marcos Escosa

  2. REPLY
    Vikram says
    February 25, 2020 at 1:41 pm

    Wats the course of the treatment wana know all on how to go about

    • REPLY
      Linda says
      March 20, 2020 at 9:35 pm

      I want to know too. My husband has gbm dx 4/16/18

  3. REPLY
    Brian Fox says
    June 13, 2020 at 10:43 am

    Sir,
    My 25-year-old son recently had surgery for GBM and is now in radiation/chemo. Is this treatment with clemastine an approved therapy? Have any patients tried it? Results? At what dose/schedule? I would appreciate any information you may have on clemastine treatment. Thanks so much.

  4. REPLY
    soada says
    June 21, 2020 at 7:52 am

    Hello. My father has glioblastoma in stage 4. I am hopeless because doctors give me very little hope for my father’s life. I wanted to know your opinion about this disease. Please give me an opinion

    • REPLY
      Katie B Zorena says
      July 17, 2020 at 3:06 am

      Soada, join GBM Survivors to Thrivers group on FB. My Mom is a 4 Year GBM Survivor.

    • REPLY
      Mike Stanley says
      June 19, 2021 at 2:11 am

      Please see my post below with a lot of info. It is a nasty disease and the treatment is rough. I am 50 now, 48 when diagnosed. Look into the medical marijuana to help him get through the treatments as well as possible.
      I would always suggest a second opinion at least on this type of diagnosis. I have had 4. A lot of cancer centers will give an online opinion.
      UPMC Hillman center is where I am now..dr Drappatz is a great doctor and person. His staff is also great.
      I started out at Allegheny General Hospital in Pittsburgh.
      After my initial surgery in 2019, I went to Dana farber institute in Boston. The doctor that reviewed my case and met with me was on the team for Ted Kennedy. He told me that my surgeon, Dr Lee, could not have done better with the surgery. He also recommended dr Drappatz and said he is the doctor I want to see for this cancer.
      I also had an opinion from Duke. This was all done online and through email. Filled out a ton of paperwork and had to get all the medical records sent to them. There are others, but I stopped here since there was really nobody saying any different.
      Let me know if you have any specific questions.

  5. REPLY
    Martha says
    June 22, 2020 at 10:49 am

    My sister has recently had surgery for GBM and is currently undergoing radition/chemo treatments. Would appreciate any info on this treatment.

    • REPLY
      Katie B Zorena says
      July 17, 2020 at 3:06 am

      Join GBM Survivors to Thrivers group on FB. My Mom is a 4 Year GBM Survivor.

    • REPLY
      Mike Stanley says
      June 19, 2021 at 1:48 am

      I was diagnosed in feb 2018 and have had 3 surgeries now and potentially another one on the horizon.
      The chemo and radiation are nasty but seem to be necessary. I had 42 days of chemo and 30 days of radiation approximately 30 days after surgery. I ate as healthy as possible and that gets harder the longer you go. I had a salad every day almost. With spinach, broccoli, red peppers, carrots, and anything else I could stomach in the salad.
      I have also used medical marijuana since I started this whole adventure. I would definitely suggest to take advantage of that if it is available to you. There is something for nausea, something for helping you to sleep, and another one I take nightly that has shown to potentially help treat and heal. This one is called Rick Simpson oil. It is expensive but I have made it past the stats that say most don’t make it more than 12-15 months. I am at almost 28 months and am working to re write the stats. Exercise is also very important in my opinion. Don’t overdue it, but keep as active as possible. Maybe a couple miles walking as many days as you can. Sleep and rest is also very important. You have to find the right amount with trial and error. I need around 7 hours to feel ok the next day and be able to function.
      I also take Ritalin that my oncologist prescribed for me to combat the fatigue caused by the treatments. This gives me enough energy to get through the day. I highly recommend this also. He started me at a low dose and worked it up until I felt like it was helping me.
      Let me know if you have any questions.

Post a comment

National Foundation for Cancer Research(NFCR) is a 501(c)(3) tax-exempt nonprofit organization.
Tax ID #: 04-2531031

Links

Contact Us

Donor Portal

© Copyright 2022 National Foundation for Cancer Research. All Rights Reserved.